Hydrogel platform with tunable stiffness based on magnetic nanoparticles cross-linked GelMA for cartilage regeneration and its intrinsic biomechanism

Cartilage injury affects numerous individuals, but the efficient repair of damaged cartilage is still a problem in clinic. Hydrogel is a potent scaffold candidate for tissue regeneration, but it remains a big challenge to improve its mechanical property and figure out the interaction of chondrocytes and stiffness. Herein, a novel hybrid hydrogel with tunable stiffness was fabricated based on methacrylated gelatin (GelMA) and iron oxide nanoparticles (Fe₂O₃) through chemical bonding. The stiffness of Fe₂O₃/GelMA hybrid hydrogel was controlled by adjusting the concentration of magnetic nanoparticles. The hydrogel platform with tunable stiffness modulated its cellular properties including cell morphology, microfilaments and Young's modulus of chondrocytes. Interestingly, Fe₂O₃/GelMA hybrid hydrogel promoted oxidative phosphorylation of mitochondria and facilitated catabolism of lipids in chondrocytes. As a result, more ATP and metabolic materials generated for cellular physiological activities and organelle component replacements in hybrid hydrogel group compared to pure GelMA hydrogel. Furthermore, implantation of Fe₂O₃/GelMA hybrid hydrogel in the cartilage defect rat model verified its remodeling potential. This study provides a deep understanding of the bio-mechanism of Fe₂O₃/GelMA hybrid hydrogel interaction with chondrocytes and indicates the hydrogel platform for further application in tissue engineering.